The goal of Core 1 is to provide mass spectrometry-based proteomic platforms for global and targeted characterization of HIV and host proteins in support of the aims and efforts for Projects 1-7 of the HARC Center. We are continuously developing new innovative strategies and improvements for more sensitive and quantitative analysis of protein abundance and posttranslational modifications, as well as for protein-protein interactions (PPIs) and protein structure determination. Our affinity-purification mass spectrometry (AP-MS) capabilities, along with newly developed proximity-based biotinylation (APEX-MS) and cross-linking mass spectrometry (XL-MS) platforms, will aid research in Projects 1-6 through interaction network mapping for Vif, Vpu, Nef, Tat, and Rev proteins in the context of HIV infection, as well as new factors identified through our unique evolutionary analysis in Project 7. Also, our new global PTM analyses pipeline will provide direct support for researchers in Projects 2, 3 and 5, focused on Vif, Vpu and Tat, respectively. Core 1 will work closely with Core 5, which will focus on computationally analyzing all the proteomic data generated. In addition, our XL-MS capabilities will also collaborate with Core 5 for structural determination and protein- interface mapping analysis for Projects 1, 3, 4 and 5. The expertise, highly sensitive MS-analysis, and ongoing innovations provided by Core 1 will continue to serve and adapt to the needs of Projects and Cores of the HARC Center.